The effort of the past year has focussed on a number of aspects regarding the relationship of products of activated lymphocytes and the cells which produce them and the cells upon which they operate. While it is clear that both B- and T-lymphocytes are capable of producing MIF and other mediators, if the in vitro tests were to have any immunological significance, it had to be established whether their production by B-cells was T-cell dependent or independent. Studies using genetic and non-responder guinea pigs, known to have a T-cell deficit, indicated MIF production required immunocompetent T-cells, and is therefore a T-cell dependent response. Thus the in vitro assays at a qualitative level detect T-cell function, although the quantitative aspects do not reflect the relative contributions of T- and B-cells. In addition, efforts were directed at understanding the fundamental regulatory mechanisms of the macrophage. Using a cloned transformed macrophage-like cell line, the mechanism of phagocytosis was studied using genetic techniques. A selection strategy was devised against phagocytic cells, and a series of variants or mutants defective or deficient in phagocytosis of antibody coated erythrocytes were derived. All variants in Fc mediated phagocytosis, however, were capable of phagocytosing latex. The defect in some, but not all, of the phagocytosis variants could be corrected by addition of cAMP. The results demonstrate that phagocytosis of E(IgG) and latex occur by distinct mechanisms and suggest that a genetic approach may provide useful insight into the various steps underlying phagocytosis and other macrophage functions. BIBLIOGRAPHIC REFERENCES: Yvonne Kress, Barry R. Bloom, Murray Wittner, Adam Rowen and H. Tanowitz. Resistance of Trypanosoma cruzi to Killing by Macrophages. Nature 257: 394-396, 1975. Barry R. Bloom, Anna Senik, Gerald Stoner, Grace Ju, Maja Nowakowski and Shogo Kano. Studies on the interaction Between Viruses and Lymphocytes. 1976 Symposia on Quantitative Biology, Volume XLI: Origins of Lymphocyte Diversity.